Biological and molecular targets for targeted therapy in colorectal cancer (literature review)

Abstract

Colon and rectal cancer are often grouped together and generally classified as colorectal cancer (CRC), despite their different clinical behaviors and treatment needs. CRC accounts for approximately 10 % of all cancers and is the second cause of cancer death. Clinical manifestations of metastatic CRC occur in approximately 20 % of patients. About 50 % of patients with loca­lized disease will eventually develop metastases. Considerable effort has been made to uncover and investigate the mutational landscape of metastatic colorectal cancer. The effect of tumor location on patient survival and response to therapy has been shown in large clinical trials; understanding that the right colon has a different embryological origin and blood supply than the left colon and the rectum became one of the key factors in choosing an approach to diagnosis and treatment of two fundamentally different diseases of the same organ. However, the underlying tumor biology that explains these differences has also been systematically investigated. As a result, four consensus molecular subtypes were identified, which are based on the anatomical location and selection of molecular markers that can act as potential targets and be used to develop individual treatment methods for each patient. In fact, the molecular stratification on which the current treatment algorithm for metastatic colorectal cancer is based is a significant step for a broader clinical understanding of genetic profiling in order to implement more effective therapeutic approaches. This resulted in a significant improvement of metastatic colorectal cancer control and patient survival. In this review, we attempt to systematize the data and summarize current knowledge about clinical and molecular differences between right- and left-sided colon cancer, which improve the therapy for metastatic colorectal cancer in the era of precision medicine.